Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00110266
• Collaborator: (none)
• Enrollment: 176
• Locations: 48
• Arm: 1
• Actual Duration (Months): 32.1
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; Iron Overload	Drug: Deferasirox	Phase 2

Detailed Description

Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 176 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-risk and INT-1, Myelodysplastic Patients Using Serum Ferritin Monitoring
• Actual Study Start Date: Jul 25, 2005
• Actual Primary Completion Date: Mar 28, 2008
• Actual Study Completion Date: Mar 28, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ICL670 Evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS	Drug: Deferasirox; 20 mg/kg/day over one year in patients with MDS; Other Names: ICL670A chelator desferal iron chelation

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting Adverse Events [up to 53 Weeks]

   Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

Secondary Outcome Measures

1. Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 [From Baseline to Weeks 13, 25, 37 and 53]

   Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).

2. Change in Labile Plasma Iron (LPI) [From Baseline to Weeks 13, 25, 37 and 49]

   LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe

3. Directly Chelatable Iron (DCI) [From Baseline to Weeks 13, 25, 37 and 49]

   The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.

4. Total Iron Levels [From Baseline to Weeks 13, 25, 37, 49 and 53]

   Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.

5. Serum Transferrin Levels [From Baseline to Weeks 13, 25, 37, 49 and 53]

   Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.

6. Transferrin Saturation [From Baseline to Weeks 13, 25, 37, 49 and 53]

   Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.

7. Transfusion Requirements [up to 1 year]

   Number of participants receiving transfusions, the summarized during the study.

8. Frequency of Hematologic Improvement During the Study [up to 1 year]

   Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase & absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.

9. Trough Plasma Deferasirox Concentration [At Week 13, 25, 37 and 49]

   The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.

10. Treatment Compliance to Deferasirox [up to 1 year]

    Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.

11. The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations [up to Week 13 (Month 3)]

    HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients with low or intermediate (INT-1) risk MDS

• Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).

• Age greater than or equal to 18 years

• Availability of transfusion records for the 12 weeks prior to registration

• A lifetime minimum of 30 previous packed red blood cell transfusions

• Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration

• Serum Ferritin:

For entry into the screening period, serum ferritin ≥ 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year.

Serum ferritin ≥ 1000 ng/mL at screening via the central lab.

• Life expectancy ≥ 6 months

• Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)

• Able to provide written informed consent

Exclusion Criteria:

• Serum creatinine above the upper limit of normal

• Alanine aminotransferase (ALT) > 500 U/L during screening

• Clinical or laboratory evidence of active Hepatitis B or C

• Urinary protein/creatinine ratio > 0.5 mg/mg

• History of HIV positive test result (ELISA or Western blot)

• Eastern Cooperative Oncology Group (ECOG) Performance Status > 2

• Patients with uncontrolled systemic hypertension

• Unstable cardiac disease not controlled by standard medical therapy

• Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation

• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment

• Pregnancy or breast feeding

• Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug

• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama Birmingham	Birmingham	Alabama	United States	35294
2	Mayo Clinic	Phoenix	Arizona	United States	85054
3	Bay Area Cancer Research Group	Concord	California	United States	94520
4	City of Hope National Medical Center	Duarte	California	United States	91010
5	Cedars-Sinai Medical Center, UCLA School of Medicine	Los Angeles	California	United States	90048
6	UCLA Medical Center	Los Angeles	California	United States	90095-1678
7	UCSF	San Francisco	California	United States	94143-0324
8	UCSF	San Francisco	California	United States	94143
9	Rocky Mountain Cancer Centers	Aurora	Colorado	United States	80012
10	Mayo Clinic	Jacksonville	Florida	United States	32224
11	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia	United States	30322
12	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
13	Novartis Investigative Site	Chicago	Illinois	United States	60612
14	University of Chicago Hospital	Chicago	Illinois	United States	60637-1470
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
16	University of Kentucky College of Medicine, Markey Cancer Center	Lexington	Kentucky	United States	40536-0093
17	Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital	Alexandria	Louisiana	United States	71301
18	St. Agnes HealthCare	Baltimore	Maryland	United States	21231-1000
19	Rush Cancer Institute Univ. of Massachussets Medical Center	Worcester	Massachusetts	United States	01605
20	Novartis Investigative Site	Southfield	Michigan	United States	48075
21	Mayo Clinic	Rochester	Minnesota	United States	55905
22	The Center for Cancer Care & Research (TCCCR)	Saint Louis	Missouri	United States	63110
23	Oncology Hematology West, PC	Omaha	Nebraska	United States	68124-2346
24	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0001
25	The Cancer Center at Hackensack University	Hackensack	New Jersey	United States	07601
26	NMOHC	Albuquerque	New Mexico	United States	87109
27	Roswell Park Cancer Center	Buffalo	New York	United States	14623
28	Rochester General Hospital/Lipson Cancer and Blood Center	Rochester	New York	United States	14621
29	Cancer Care of WNC	Asheville	North Carolina	United States	28801
30	Wake Forest UniversitComprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1082
31	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
32	The Ohio State University	Columbus	Ohio	United States	43210
33	Novartis Investigative Site	Portland	Oregon	United States	97239
34	Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center	Philadelphia	Pennsylvania	United States	19107
35	Western Pennsylvania Hospital Cancer Institute	Pittsburgh	Pennsylvania	United States	15224
36	The West Cancer Clinic	Memphis	Tennessee	United States	38120
37	Novartis Investigative site	Nashville	Tennessee	United States	37232
38	Baylor/The Methodist Hospital	Houston	Texas	United States	77030
39	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
40	Arlington Fairfax Hematology Oncology PC	Arlington	Virginia	United States	22205
41	Novartis Investigative Site	Spokane	Washington	United States	99202
42	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
43	Novartis Investigative Site	Vancouver	British Columbia	Canada	V6Z 1Y6
44	Novartis Investigative Site	Hamilton	Ontario	Canada	L8N 3Z5
45	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
46	Novartis Investigative Site	Toronto	Ontario	Canada	M5g 2M9
47	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
48	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results for CICL670AUS03 from the Novartis Clinical Trials website
• Publication (Embasse # 2012421150)
• Publication (Embasse # 2012421150)

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00110266
• Other Study ID Numbers: CICL670AUS03; NCT00343837
• First Posted: May 5, 2005
• Last Update Posted: Aug 16, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Novartis Pharmaceuticals: ICL670; Deferasirox; Iron chelation; Chelator; Desferal
• Additional relevant MeSH terms: Myelodysplastic Syndromes; Iron Overload; Deferasirox

Study Results

Participant Flow

Recruitment Details	The study was conducted at 39 centers in the United States and 6 centers in Canada
Pre-assignment Detail	A total of 176 participants enrolled in the study, of these 173 participants were treated. Three of the enrolled participants were not treated as 2 withdrew the consent and 1 died even before initiating the treatment. Of the 173 treated participants, 95 completed the study and 78 discontinued treatment prematurely.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 Milligrams per Kilogram per day (mg/kg/day) orally once per day (OD) for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Period Title: Overall Study
STARTED	173
COMPLETED	95
NOT COMPLETED	78

Baseline Characteristics

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Overall Participants	173
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.9 (11.45)
Sex: Female, Male (Count of Participants)
Female	70 40.5%
Male	103 59.5%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	159 91.9%
Black	4 2.3%
Oriental	4 2.3%
Other	6 3.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Adverse Events
Description	Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
Time Frame	up to 53 Weeks

Outcome Measure Data

Analysis Population Description

The safety population consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Count of Participants [Participants]	171 98.8%

2. Secondary Outcome

Title	Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
Description	Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).
Time Frame	From Baseline to Weeks 13, 25, 37 and 53

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	172
Baseline	2771.5
Week 13	-146.5
Week 25	-167.5
Week 37	-505.0
Week 53	-592.0

3. Secondary Outcome

Title	Change in Labile Plasma Iron (LPI)
Description	LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe
Time Frame	From Baseline to Weeks 13, 25, 37 and 49

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Baseline	0.30
Week 13	-0.10
Week 25	-0.20
Week 37	-0.30
Week 49	-0.45

4. Secondary Outcome

Title	Directly Chelatable Iron (DCI)
Description	The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.
Time Frame	From Baseline to Weeks 13, 25, 37 and 49

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Baseline	0.00
Week 13	0.00
Week 25	0.00
Week 37	0.00
Week 49	0.00

5. Secondary Outcome

Title	Total Iron Levels
Description	Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.
Time Frame	From Baseline to Weeks 13, 25, 37, 49 and 53

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Baseline	194.0
Week 13	230.50
Week 25	222.0
Week 37	212.0
Week 49	218.0
Week 53	221.00

6. Secondary Outcome

Title	Serum Transferrin Levels
Description	Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.
Time Frame	From Baseline to Weeks 13, 25, 37, 49 and 53

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Baseline	156.0
Week 13	161.0
Week 25	160.0
Week 37	158.0
Week 49	160.0
Week 53	161.00

7. Secondary Outcome

Title	Transferrin Saturation
Description	Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.
Time Frame	From Baseline to Weeks 13, 25, 37, 49 and 53

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Baseline	91.00
Week 13	-11.00
Week 25	-11.00
Week 37	-12.50
Week 49	-12.00
Week 53	-18.00

8. Secondary Outcome

Title	Transfusion Requirements
Description	Number of participants receiving transfusions, the summarized during the study.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Screening	163 94.2%
Week 1 through 13	136 78.6%
Week 14 through 26	119 68.8%
Week 27 through 39	98 56.6%
Week 40 through 52	72 41.6%

9. Secondary Outcome

Title	Frequency of Hematologic Improvement During the Study
Description	Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase & absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

The analysis was performed on Per protocol population defined as number of participants who did not present any major deviations from protocol and received at least one dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	91
Response (Yes)	7 4%
Response (No)	74 42.8%
Missing	10 5.8%

10. Secondary Outcome

Title	Trough Plasma Deferasirox Concentration
Description	The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.
Time Frame	At Week 13, 25, 37 and 49

Outcome Measure Data

Analysis Population Description

The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
Week 13	21.200
Week 25	26.700
Week 37	25.200
Week 49	30.700

11. Secondary Outcome

Title	Treatment Compliance to Deferasirox
Description	Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	173
20 to < 40 %	2 1.2%
40 - < 60 %	1 0.6%
60 - < 80 %	4 2.3%
80 - < 100 %	89 51.4%
100 - < 120 %	65 37.6%
≥ 120 %	12 6.9%

12. Secondary Outcome

Title	The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
Description	HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.
Time Frame	up to Week 13 (Month 3)

Outcome Measure Data

Analysis Population Description

The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	94
Negative	85 49.1%
Positive Heterozygous	9 5.2%
Negative	70 40.5%
Positive Heterozygous	24 13.9%
Negative	92 53.2%
Positive Heterozygous	2 1.2%

Adverse Events

Time Frame	All Adverse Event Were Collected From Start of Treatment up to 53 Weeks
Adverse Event Reporting Description	Out of 176 participants enrolled in the study, 173 participants received study medication. As, two participants withdrew consent and one died before initiating the treatment, were not considered for this analysis. The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Arm/Group Title	Deferasirox		Enrolled, Not Treated
Arm/Group Description	Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.		Participant died before initiating the treatment.
All Cause Mortality
	Deferasirox		Enrolled, Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/173 (9.8%)		1/3 (33.3%)
Serious Adverse Events
	Deferasirox		Enrolled, Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/173 (45.1%)		0/3 (0%)
Blood and lymphatic system disorders
Anaemia	4/173 (2.3%)		0/3 (0%)
Febrile neutropenia	7/173 (4%)		0/3 (0%)
Haemolytic anaemia	1/173 (0.6%)		0/3 (0%)
Neutropenia	1/173 (0.6%)		0/3 (0%)
Splenic infarction	1/173 (0.6%)		0/3 (0%)
Thrombocytopenia	4/173 (2.3%)		0/3 (0%)
Cardiac disorders
Atrial fibrillation	1/173 (0.6%)		0/3 (0%)
Atrial flutter	1/173 (0.6%)		0/3 (0%)
Cardiac arrest	1/173 (0.6%)		0/3 (0%)
Cardiac failure congestive	4/173 (2.3%)		0/3 (0%)
Cardio-respiratory arrest	2/173 (1.2%)		0/3 (0%)
Cardiomyopathy	1/173 (0.6%)		0/3 (0%)
Myocardial infarction	1/173 (0.6%)		0/3 (0%)
Pericardial effusion	1/173 (0.6%)		0/3 (0%)
Ventricular tachycardia	1/173 (0.6%)		0/3 (0%)
Eye disorders
Blindness	1/173 (0.6%)		0/3 (0%)
Eyelid oedema	1/173 (0.6%)		0/3 (0%)
Vision blurred	1/173 (0.6%)		0/3 (0%)
Gastrointestinal disorders
Abdominal pain	1/173 (0.6%)		0/3 (0%)
Abdominal pain upper	1/173 (0.6%)		0/3 (0%)
Constipation	1/173 (0.6%)		0/3 (0%)
Diarrhoea	5/173 (2.9%)		0/3 (0%)
Dysphagia	1/173 (0.6%)		0/3 (0%)
Gastrointestinal haemorrhage	3/173 (1.7%)		0/3 (0%)
Ileus	1/173 (0.6%)		0/3 (0%)
Intestinal perforation	1/173 (0.6%)		0/3 (0%)
Nausea	3/173 (1.7%)		0/3 (0%)
Rectal haemorrhage	1/173 (0.6%)		0/3 (0%)
Vomiting	3/173 (1.7%)		0/3 (0%)
General disorders
Asthenia	1/173 (0.6%)		0/3 (0%)
Chest pain	2/173 (1.2%)		0/3 (0%)
Concomitant disease progression	3/173 (1.7%)		0/3 (0%)
Fatigue	1/173 (0.6%)		0/3 (0%)
Induration	1/173 (0.6%)		0/3 (0%)
Malaise	1/173 (0.6%)		0/3 (0%)
Multi-organ failure	1/173 (0.6%)		0/3 (0%)
Oedema peripheral	5/173 (2.9%)		0/3 (0%)
Pyrexia	7/173 (4%)		0/3 (0%)
Hepatobiliary disorders
Cholecystitis	1/173 (0.6%)		0/3 (0%)
Cholecystitis acute	1/173 (0.6%)		0/3 (0%)
Hyperbilirubinaemia	1/173 (0.6%)		0/3 (0%)
Jaundice cholestatic	1/173 (0.6%)		0/3 (0%)
Immune system disorders
Drug hypersensitivity	2/173 (1.2%)		0/3 (0%)
Infections and infestations
Bacteraemia	2/173 (1.2%)		0/3 (0%)
Bacterial sepsis	1/173 (0.6%)		0/3 (0%)
Cellulitis	6/173 (3.5%)		0/3 (0%)
Cholecystitis infective	1/173 (0.6%)		0/3 (0%)
Clostridial infection	2/173 (1.2%)		0/3 (0%)
Clostridium bacteraemia	1/173 (0.6%)		0/3 (0%)
Escherichia sepsis	1/173 (0.6%)		0/3 (0%)
Liver abscess	1/173 (0.6%)		0/3 (0%)
Lobar pneumonia	2/173 (1.2%)		0/3 (0%)
Pharyngeal abscess	1/173 (0.6%)		0/3 (0%)
Pneumonia	12/173 (6.9%)		0/3 (0%)
Propionibacterium infection	1/173 (0.6%)		0/3 (0%)
Pseudomonal bacteraemia	1/173 (0.6%)		0/3 (0%)
Sepsis	3/173 (1.7%)		0/3 (0%)
Septic shock	2/173 (1.2%)		0/3 (0%)
Staphylococcal abscess	1/173 (0.6%)		0/3 (0%)
Staphylococcal infection	1/173 (0.6%)		0/3 (0%)
Urinary tract infection	5/173 (2.9%)		0/3 (0%)
Urinary tract infection enterococcal	1/173 (0.6%)		0/3 (0%)
Urosepsis	1/173 (0.6%)		0/3 (0%)
Wound infection staphylococcal	1/173 (0.6%)		0/3 (0%)
Injury, poisoning and procedural complications
Femur fracture	1/173 (0.6%)		0/3 (0%)
Hip fracture	4/173 (2.3%)		0/3 (0%)
Post procedural haemorrhage	1/173 (0.6%)		0/3 (0%)
Spinal compression fracture	1/173 (0.6%)		0/3 (0%)
Subdural haematoma	2/173 (1.2%)		0/3 (0%)
Transfusion reaction	1/173 (0.6%)		0/3 (0%)
Metabolism and nutrition disorders
Anorexia	1/173 (0.6%)		0/3 (0%)
Dehydration	5/173 (2.9%)		0/3 (0%)
Fluid overload	1/173 (0.6%)		0/3 (0%)
Haemochromatosis	1/173 (0.6%)		0/3 (0%)
Hypercalcaemia	1/173 (0.6%)		0/3 (0%)
Hypoglycaemia	1/173 (0.6%)		0/3 (0%)
Hyponatraemia	1/173 (0.6%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate	1/173 (0.6%)		0/3 (0%)
Costochondritis	1/173 (0.6%)		0/3 (0%)
Flank pain	2/173 (1.2%)		0/3 (0%)
Muscular weakness	1/173 (0.6%)		0/3 (0%)
Pain in extremity	1/173 (0.6%)		0/3 (0%)
Tendonitis	1/173 (0.6%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	2/173 (1.2%)		0/3 (0%)
Chronic myelomonocytic leukaemia	1/173 (0.6%)		0/3 (0%)
Gastric cancer	1/173 (0.6%)		0/3 (0%)
Malignant melanoma	1/173 (0.6%)		0/3 (0%)
Myelodysplastic syndrome	1/173 (0.6%)		0/3 (0%)
Nervous system disorders
Convulsion	1/173 (0.6%)		0/3 (0%)
Dizziness	2/173 (1.2%)		0/3 (0%)
Haemorrhage intracranial	1/173 (0.6%)		0/3 (0%)
Presyncope	1/173 (0.6%)		0/3 (0%)
Syncope	1/173 (0.6%)		0/3 (0%)
Transient ischaemic attack	1/173 (0.6%)		0/3 (0%)
Psychiatric disorders
Confusional state	1/173 (0.6%)		0/3 (0%)
Renal and urinary disorders
Acute prerenal failure	1/173 (0.6%)		0/3 (0%)
Dysuria	1/173 (0.6%)		0/3 (0%)
Haematuria	1/173 (0.6%)		0/3 (0%)
Renal failure acute	6/173 (3.5%)		0/3 (0%)
Renal impairment	1/173 (0.6%)		0/3 (0%)
Reproductive system and breast disorders
Prostatic haemorrhage	1/173 (0.6%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/173 (0.6%)		0/3 (0%)
Cough	1/173 (0.6%)		0/3 (0%)
Dyspnoea	4/173 (2.3%)		0/3 (0%)
Dyspnoea at rest	1/173 (0.6%)		0/3 (0%)
Dyspnoea exertional	1/173 (0.6%)		0/3 (0%)
Hypoxia	2/173 (1.2%)		0/3 (0%)
Lung infiltration	2/173 (1.2%)		0/3 (0%)
Pleural effusion	1/173 (0.6%)		0/3 (0%)
Pulmonary congestion	1/173 (0.6%)		0/3 (0%)
Pulmonary embolism	1/173 (0.6%)		0/3 (0%)
Pulmonary oedema	1/173 (0.6%)		0/3 (0%)
Respiratory distress	1/173 (0.6%)		0/3 (0%)
Respiratory failure	3/173 (1.7%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Rash macular	1/173 (0.6%)		0/3 (0%)
Rash papular	1/173 (0.6%)		0/3 (0%)
Rash pruritic	1/173 (0.6%)		0/3 (0%)
Urticaria	1/173 (0.6%)		0/3 (0%)
Vascular disorders
Aneurysm	1/173 (0.6%)		0/3 (0%)
Deep vein thrombosis	1/173 (0.6%)		0/3 (0%)
Haemorrhage	1/173 (0.6%)		0/3 (0%)
Lymphorrhoea	1/173 (0.6%)		0/3 (0%)
Peripheral vascular disorder	1/173 (0.6%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Deferasirox		Enrolled, Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	166/173 (96%)		0/3 (0%)
Blood and lymphatic system disorders
Anaemia	4/173 (2.3%)		0/3 (0%)
Neutropenia	9/173 (5.2%)		0/3 (0%)
Splenomegaly	7/173 (4%)		0/3 (0%)
Thrombocytopenia	9/173 (5.2%)		0/3 (0%)
Cardiac disorders
Tachycardia	4/173 (2.3%)		0/3 (0%)
Eye disorders
Vision blurred	9/173 (5.2%)		0/3 (0%)
Gastrointestinal disorders
Abdominal distension	16/173 (9.2%)		0/3 (0%)
Abdominal pain	18/173 (10.4%)		0/3 (0%)
Abdominal pain upper	10/173 (5.8%)		0/3 (0%)
Constipation	30/173 (17.3%)		0/3 (0%)
Diarrhoea	101/173 (58.4%)		0/3 (0%)
Dyspepsia	17/173 (9.8%)		0/3 (0%)
Flatulence	6/173 (3.5%)		0/3 (0%)
Gastrooesophageal reflux disease	4/173 (2.3%)		0/3 (0%)
Haemorrhoids	5/173 (2.9%)		0/3 (0%)
Nausea	60/173 (34.7%)		0/3 (0%)
Stomach discomfort	4/173 (2.3%)		0/3 (0%)
Stomatitis	12/173 (6.9%)		0/3 (0%)
Vomiting	21/173 (12.1%)		0/3 (0%)
General disorders
Asthenia	12/173 (6.9%)		0/3 (0%)
Chest discomfort	8/173 (4.6%)		0/3 (0%)
Chest pain	9/173 (5.2%)		0/3 (0%)
Chills	8/173 (4.6%)		0/3 (0%)
Fatigue	68/173 (39.3%)		0/3 (0%)
Gait disturbance	5/173 (2.9%)		0/3 (0%)
Oedema	6/173 (3.5%)		0/3 (0%)
Oedema peripheral	35/173 (20.2%)		0/3 (0%)
Pain	9/173 (5.2%)		0/3 (0%)
Pyrexia	28/173 (16.2%)		0/3 (0%)
Infections and infestations
Bronchitis	4/173 (2.3%)		0/3 (0%)
Cellulitis	4/173 (2.3%)		0/3 (0%)
Cystitis	5/173 (2.9%)		0/3 (0%)
Infection	4/173 (2.3%)		0/3 (0%)
Nasopharyngitis	16/173 (9.2%)		0/3 (0%)
Pneumonia	9/173 (5.2%)		0/3 (0%)
Sinusitis	9/173 (5.2%)		0/3 (0%)
Upper respiratory tract infection	19/173 (11%)		0/3 (0%)
Urinary tract infection	17/173 (9.8%)		0/3 (0%)
Injury, poisoning and procedural complications
Contusion	14/173 (8.1%)		0/3 (0%)
Fall	4/173 (2.3%)		0/3 (0%)
Transfusion reaction	5/173 (2.9%)		0/3 (0%)
Investigations
Alanine aminotransferase increased	4/173 (2.3%)		0/3 (0%)
Blood creatinine increased	34/173 (19.7%)		0/3 (0%)
Blood urea increased	4/173 (2.3%)		0/3 (0%)
International normalised ratio increased	4/173 (2.3%)		0/3 (0%)
Weight decreased	12/173 (6.9%)		0/3 (0%)
Metabolism and nutrition disorders
Anorexia	24/173 (13.9%)		0/3 (0%)
Decreased appetite	12/173 (6.9%)		0/3 (0%)
Dehydration	4/173 (2.3%)		0/3 (0%)
Hypokalaemia	9/173 (5.2%)		0/3 (0%)
Hypomagnesaemia	4/173 (2.3%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/173 (12.1%)		0/3 (0%)
Back pain	20/173 (11.6%)		0/3 (0%)
Bone pain	5/173 (2.9%)		0/3 (0%)
Flank pain	4/173 (2.3%)		0/3 (0%)
Muscle spasms	13/173 (7.5%)		0/3 (0%)
Muscular weakness	7/173 (4%)		0/3 (0%)
Musculoskeletal pain	4/173 (2.3%)		0/3 (0%)
Myalgia	5/173 (2.9%)		0/3 (0%)
Neck pain	5/173 (2.9%)		0/3 (0%)
Pain in extremity	12/173 (6.9%)		0/3 (0%)
Nervous system disorders
Dizziness	23/173 (13.3%)		0/3 (0%)
Dysgeusia	7/173 (4%)		0/3 (0%)
Headache	21/173 (12.1%)		0/3 (0%)
Peripheral sensory neuropathy	4/173 (2.3%)		0/3 (0%)
Syncope	5/173 (2.9%)		0/3 (0%)
Psychiatric disorders
Anxiety	4/173 (2.3%)		0/3 (0%)
Confusional state	5/173 (2.9%)		0/3 (0%)
Depression	15/173 (8.7%)		0/3 (0%)
Insomnia	12/173 (6.9%)		0/3 (0%)
Renal and urinary disorders
Chromaturia	4/173 (2.3%)		0/3 (0%)
Dysuria	5/173 (2.9%)		0/3 (0%)
Haematuria	7/173 (4%)		0/3 (0%)
Nephrolithiasis	7/173 (4%)		0/3 (0%)
Pollakiuria	7/173 (4%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	21/173 (12.1%)		0/3 (0%)
Dyspnoea	36/173 (20.8%)		0/3 (0%)
Dyspnoea exertional	6/173 (3.5%)		0/3 (0%)
Epistaxis	11/173 (6.4%)		0/3 (0%)
Nasal congestion	4/173 (2.3%)		0/3 (0%)
Pharyngolaryngeal pain	18/173 (10.4%)		0/3 (0%)
Rhinorrhoea	10/173 (5.8%)		0/3 (0%)
Sinus congestion	4/173 (2.3%)		0/3 (0%)
Throat irritation	4/173 (2.3%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Dry skin	7/173 (4%)		0/3 (0%)
Ecchymosis	9/173 (5.2%)		0/3 (0%)
Hyperhidrosis	5/173 (2.9%)		0/3 (0%)
Night sweats	8/173 (4.6%)		0/3 (0%)
Petechiae	4/173 (2.3%)		0/3 (0%)
Pruritus	11/173 (6.4%)		0/3 (0%)
Rash	32/173 (18.5%)		0/3 (0%)
Skin ulcer	4/173 (2.3%)		0/3 (0%)
Urticaria	7/173 (4%)		0/3 (0%)
Vascular disorders
Hypertension	9/173 (5.2%)		0/3 (0%)
Hypotension	10/173 (5.8%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.